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Biomedical subjects

A Bugge

Publications and source records attributed to A Bugge.

16 recordsLinked to original sources
PubMed1999

Simultaneous determination of citalopram, fluoxetine, paroxetine and their metabolites in plasma and whole blood by high-performance liquid chromatography with ultraviolet and fluorescence detection.

A method for the simultaneous determination of the three selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine, paroxetine and their metabolites in whole blood and plasma was developed. Sample clean-up and separation were achieved using a solid-phase extraction method with C8 non-endcapped columns followed by reversed-phase high-performance liquid chromatography with fluorescence and ultraviolet detection. The robustness of the solid-phase extraction method was tested for citalopram, fluoxetine, paroxetine, Cl-citalopram and the internal standard, protriptyline, using a fractional factorial design with nine factors at two levels. The fractional factorial design showed two significant effects for paroxetine in whole blood. The robustness testing for citalopram, fluoxetine, Cl-citalopram and the internal standard revealed no significant main effects in whole blood and plasma. The optimization and the robustness of the high-performance liquid chromatographic separation were investigated with regard to pH and relative amount of acetonitrile in the mobile phase by a central composite design circumscribed. No alteration in the elution order and no significant change in resolution for a deviation of +/-1% acetonitrile and +/-0.3 pH units from the specified conditions were observed. The method was validated for the concentration range 0.050-5.0 micromol/l with fluorescence detection and 0.12-5.0 micromol/l with ultraviolet detection. The limits of quantitation were 0.025 micromol/l for citalopram and paroxetine, 0.050 micromol/l for desmethyl citalopram, di-desmethyl citalopram and citalopram-N-oxide, 0.12 micromol/l for the paroxetine metabolites by fluorescence detection, and 0.10 micromol/l for fluoxetine and norfluoxetine by ultraviolet detection. Relative standard deviations for the within-day and between-day precision were in the ranges 1.4-10.6% and 3.1-20.3%, respectively. Recoveries were in the 63-114% range for citalopram, fluoxetine and paroxetine, and in the 38-95% range for the metabolites. The method has been used for the analysis of whole blood and plasma samples from SSRI-exposed patients and forensic cases.

Acetonitriles↗
PubMed1993

An animal model of postmortem amitriptyline redistribution.

An experimental rat model was developed to study postmortem changes of drug concentration after an acute overdose. Overnight fasted rats were fed 75 mg of amitriptyline (AMI). Two h after dosing, the rats were anaesthetized and blood samples were drawn from the femoral vein (peripheral blood--PB) and the heart (HB). The rats were sacrificed by CO2 and left at room temperature for either 0.1, 0.5, 1, 2, 5, 10, 24, 48, or 96 hours, when samples of heart blood, blood from the inferior vena cava (PB) and tissue samples from different liver lobes, heart, lungs, kidney, thigh muscle, and brain were taken. Samples were analyzed by high performance liquid chromatography. The AMI concentration in HB increased fairly rapidly within the first 2 h postmortem and from then the average ratio was 6.4 +/- 0.8 (mean +/- sem) (n = 31). In PB, the post/antemortem AMI concentration ratio followed an approximately exponential rise; at 2 h postmortem the ratio was 1.6 +/- 0.3 (n = 5), and at 96 h 55.1 +/- 23.8 (n = 4). For the main metabolite nortriptyline (NOR), the concentration changes followed the same pattern, but to a lesser extent. Among the tissues, the liver lobes had high, but variable drug concentrations; lobes lying closest to the stomach had the highest drug concentrations. The drug concentration in the lungs declined significantly. This animal model demonstrates postmortem drug concentration changes similar to those described in humans. Probable mechanisms include drug diffusion from the stomach and GI tract to the surrounding tissues and blood; and postmortem drug release from the lungs and possibly other drug-rich tissues into the blood.

Amitriptyline↗
PubMed1992

Diffusion as a mechanism of postmortem drug redistribution: an experimental study in rats.

In some cases of drug overdose there is a reservoir of unabsorbed drug in the stomach and gut. Furthermore, agonal aspiration might establish a second reservoir in the lungs. Two experimental rat models were used to study if diffusion from these reservoirs could contribute to the phenomenon of postmortem drug redistribution. Overnight fasted rats were sacrificed by CO2 and 75 mg of amitriptyline (AMI) was administered by a gastric tube. In the first series (n = 19), the tubes were removed after AMI administration. In the second series (n = 17), the trachea was ligated and cut prior to drug administration to prevent airways contamination. The rats were left at room temperature on their back for a period of 5, 10, 24, 48, 96 up to 192 h and samples of heart blood, blood from the inferior vena cava, tissue samples from heart, lungs, different liver lobes, kidney and psoas muscle were taken. In both series of rats we observed that as early as 5 h postmortem increasing concentrations of amitriptyline were found in the liver lobes lying closest to the stomach. In rats where the trachea was not ligated, drug contamination of the lungs also resulted in an increase in drug concentration within 5 h in heart blood and heart muscle. In rats where the trachea had been ligated, amitriptyline was found in the lungs after 96 h postmortem. The main metabolite nortriptyline was also detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Amitriptyline↗
PubMed1988

A three-year prospective study of rearrests for driving under influence of alcohol or drugs.

Fifty drunken drivers and 50 drivers with high blood drug concentrations arrested during the first four months of 1983 were selected for a study of rearrests for driving under influence of alcohol or drugs. Of the drugged drivers selected, 32 had been driving with high blood concentrations of diazepam (greater than 1.0 microM). 50% of these drivers were rearrested during the subsequent three years. The rearrest rate was low (6%) among those who had been driving with high blood concentrations of amphetamine (greater than 2.0 microM) or THC (greater than 0.010 microM). Among the drunken drivers arrested (BAC greater than 0.05%), the rearrest rate was 20%. The drivers were mostly rearrested for driving under the influence of alcohol.

Adult↗
PubMed1987

A retrospective study of drugged driving in Norway.

The National Institute of Forensic Toxicology, Oslo, receives blood and urine samples from all Norwegian drivers apprehended on suspicion of driving under the influence of alcohol or drugs. In 1983 we received samples from 1446 drug-suspected drivers, out of which 445 underwent toxicological analysis. The drugs found most frequently were tetrahydrocannabinol (THC) (n = 199), diazepam (n = 166) and amphetamine (n = 102). A cautious interpretation of the data indicate that about 200 of the 445 subjects selected for toxicological analysis drove under severe influence of drugs. Because of the high percentage of submitted cases not analysed for drugs, this figure represents a minimum estimate. Compared with the results from 1978, we found a several-fold increase in detections of THC and amphetamine in 1983. The number of diazepam detections did not increase in a similar way, but we estimated that the diazepam detections would have increased 3-fold if we had analysed as frequent for this drug in 1983 as in 1978.

Adolescent↗
PubMed1986

Determination of succinyldicholine in different tissue samples from guinea pigs after injection of a single intravenous dose.

The distribution and postmortem stability of succinyldicholine in different tissues and urine from guinea-pigs has been studied. Succinyldicholine was extracted from tissue homogenates and urine samples from animals sacrificed by intravenous injections of succinyldicholine hydrochloride (40 mg/kg). The bis-quaternary ammonium compound was demethylated and the tertiary amine was analysed by gas chromatography/mass spectrometry. The concentrations found in muscle, kidney and urine were often low; in muscle below 5 pmol/g, in kidney from 5 to 1500 pmol/g and in urine from 5 to 650 pmol/ml. The eye proved to be the best tissue sample, with a rather high and constant concentration (280 +/- 36 pmol/g) of succinyldicholine. The postmortem stability was studied by storing the bodies at 4 degrees C. After 6 days storage the drug concentrations in the eyes started to decline. Four weeks after death it was not possible to detect any succinyldicholine in this tissue.

Animals↗
PubMed1985

Cannabinoids in blood and urine after passive inhalation of Cannabis smoke.

To test the possibility that cannabinoids are detectable following passive inhalation of Cannabis smoke the following study was performed. Five healthy volunteers who had previously never used Cannabis, passively inhaled Cannabis smoke for 30 min. Cannabis smoke was provided by other subjects smoking either marijuana or hashish cigarettes in a small closed car, containing approximately 1650 L of air. delta 9-Tetrahydrocannabinol (THC) could be detected in the blood of all passive smokers immediately after exposure in concentrations ranging from 1.3 to 6.3 ng/mL. At the same time total blood cannabinoid levels (assayed by radioimmunoassay [RIA] ) were higher than 13 ng/mL in four of the volunteers. Both THC and cannabinoid blood concentrations fell close to the cutoff limits of the respective assays during the following 2 h. Passive inhalation also resulted in the detection of cannabinoids in the urine by RIA and enzyme multiple immunoassay technique (EMIT) assays (above 13 and 20 ng/mL, respectively). It is concluded that the demonstration of cannabinoids in blood or urine is no unequivocal proof of active Cannabis smoking.

Adult↗
PubMed1981

Cis(Z)-clopenthixol and clopenthixol in the treatment of acute psychoses and exacerbations of chronic psychoses. A double-blind clinical investigation.

The clinical effect of cis(Z)-clopenthixol has been compared with that of clopenthixol, which is a mixture of the pharmacologically active cis(Z)-isomer and the inactive trans(E)-isomer. In the 4-week double-blind trial were included 20 patients with acute psychoses and exacerbations of chronic psychoses, mainly schizophrenics. Ratings evaluating severity of illness, therapeutic effect, possible interference of side effects with the patient's functioning were done at weeks 0, 2, and 4, at which occasions also the BPRS was filled in. All patients improved, most of them so much that their final BPRS-score was less than half their initial score. In conclusion, the antipsychotic effect of cis(Z)-clopenthixol was found equal to that of clopenthixol whereas the cis(Z)-isomer on a mg/mg basis was twice as active as clopenthixol. Side effects were few, similar, and equally frequent in the two groups, extrapyramidal side effects and drowsiness being the most common.

Adult↗
PubMed1976

Quantitative high-performance liquid chromatography of diazepam and N-desmethyldiazepam in blood.

High-performance liquid chromatography on porous silica has been employed to determine diazepam and N-desmethyldiazepam in human blood. For forensic purposes, 1.0 ml of blood is sufficient for a quantitative determination of the benzodiazepines in concentrations above 100 ng/ml. In cases where lower levels, 25-100 ng/ml, are of interest, 2.0 ml of blood together with a somewhat more elaborate extraction procedure are necessary.

Chromatography, High Pressure Liquid↗
PubMed1975

Noxiptilin (Agedal)--a new tricyclic antidepressant with a faster onset of action? A double-blind, multicentre comparison with amitriptyline.

Five psychiatric hospitals in Norway took part in this double blind clinical trial, in which noxiptilin (Agedal) was compared with amitriptyline in hospitalized patients with primary depressive illness. According to total randomization, each patient received either noxiptilin or amitriptyline in semiflexible dosage, usually to a maximum dialy dose of 200-250 mg, for at least three, and possibly six weeks. Thirty patients received noxiptilin and 32 received amitriptyline for at least three weeks. The "total" improvement was assessed in two different ways: 1) By direct global assessment; according to this method, there was a non-significant tendency towards greater improvement on amitriptyline after three and sex weeks, in female and male patients alike. 2) By percentage reduction in total score on Hamilton's rating scale for depression; according to this method, there was a significantly greater improvement on noxiptilin after one week in female but not in male patients. After 2, 3 and 6 weeks there were no significant differences. Thus, this trial seems to support earlier claims that noxiptilin has a faster onset of action than amitriptyline. The two drugs did not differ significantly in their effect on any single symptom, nor in their effect on different types of depression. Both drugs had a better effect in patients with duration of present illness less than three months, than in patients with a duration longer than three months. Noxiptilin had a significantly better effect than amitriptyline in patients with insidious onset of present illness, whereas there was a strong (but non-significant) tendency for a better effect of amitriptyline in patients with a more acute onset of illness. No satisfactory explanation can be offered for this unexpected finding.

Adult↗
PubMedDate not supplied

Interference with analysis of amphetamine in blood by N-ethylbenzenamine from rubber septums.

When blood stored in glass vials sealed with natural rubber septums was screened for amphetamine, a contaminant was seen. The contamination originated from the rubber septums and was identified by GC/MS as N-ethylbenzenamine. Like amphetamine, N-ethylbenzenamine was extracted from strongly alkaline solutions. N-Ethylbenzenamine and amphetamine chromatographed with the same retention time on a packed Apiezon/KOH column and on nonpolar capillary columns. Separation was achieved on a medium polar capillary column. Trifluoroacetyl derivatives of amphetamine and N-ethylbenzenamine had the same retention time on a packed SP-2250 column, but separated on nonpolar capillary columns. The amounts of N-ethylbenzenamine found were high enough to give rise to significant false positive results if N-ethylbenzenamine was erroneously read as amphetamine. N-Ethylbenzenamine is believed to be formed by thermal decomposition of the vulcanizing agent zinc ethylphenyldithiocarbamate used in rubber production.

Amphetamine↗